The present invention relates generally to the treatment of spinal diseases and injuries, and more specifically to the restoration of the spinal disc following the treatment. The invention contemplates devices and methods for restoring the normal intervertebral disc space height and for facilitating the introduction of biomaterials for use in the repair and restoration of the intervertebral disc.
The intervertebral disc is divided into two distinct regions: the nucleus pulposus and the annulus fibrosus. The nucleus lies at the center of the disc and is surrounded and contained by the annulus. The annulus contains collagen fibers that form concentric lamellae that surround the nucleus and insert into the endplates of the adjacent vertebral bodies to form a reinforced structure. Cartilaginous endplates are located at the interface between the disc and the adjacent vertebral bodies.
The intervertebral disc is the largest avascular structure in the body. The cells of the disc receive nutrients and expel waste by diffusion through the adjacent vascularized endplates. The hygroscopic nature of the proteoglycan matrix secreted by cells of the nucleus operates to generate high intra-nuclear pressure. As the water content in the disc increases, the intra-nuclear pressure increases and the nucleus swells to increase the height of the disc. This swelling places the fibers of the annulus in tension. A normal disc has a height of about 10-15 mm.
There are many causes of disruption or degeneration of the intervertebral disc that can be generally categorized as mechanical, genetic and biochemical. Mechanical damage includes herniation in which a portion of the nucleus pulposus projects through a fissure or tear in the annulus fibrosus. Genetic and biochemical causes can result in changes in the extracellular matrix pattern of the disc and a decrease in biosynthesis of extracellular matrix components by the cells of the disc. Degeneration is a progressive process that usually begins with a decrease in the ability of the extracellular matrix in the central nucleus pulposus to bind water due to reduced proteoglycan content. With a loss of water content, the nucleus becomes desiccated resulting in a decrease in internal disc hydraulic pressure, and ultimately to a loss of disc height. This loss of disc height can cause the annulus to buckle with non-tensile loading and the annular lamellae to delaminate, resulting in annular fissures. Herniation may then occur as rupture leads to protrusion of the nucleus.
Proper disc height is necessary to ensure proper functionality of the intervertebral disc and spinal column. The disc serves several functions, although its primary function is to facilitate mobility of the spine. In addition, the disc provides for load bearing, load transfer and shock absorption between vertebral levels. The weight of the person generates a compressive load on the discs, but this load is not uniform during typical bending movements. During forward flexion, the posterior annular fibers are stretched while the anterior fibers are compressed. In addition, a translocation of the nucleus occurs as the center of gravity of the nucleus shifts away from the center and towards the extended side.
Changes in disc height can have both local and global effects. On the local (or cellular, level) decreased disc height results in increased pressure in the nucleus, which can lead to a decrease in cell matrix synthesis and an increase in cell necrosis and apoptosis. In addition, increases in intra-discal pressure create an unfavorable environment for fluid transfer into the disc, which can cause a further decrease in disc height.
Decreased disc height also results in significant changes in the global mechanical stability of the spine. With decreasing height of the disc, the facet joints bear increasing loads and may undergo hypertrophy and degeneration, and may even act as a source of pain over time. Decreased stiffness of the spinal column and increased range of motion resulting from loss of disc height can lead to further instability of the spine, as well as back pain. The outer annulus fibrosus is designed to provide stability under tensile loading, and a well-hydrated nucleus maintains sufficient disc height to keep the annulus fibers properly tensioned. With decreases in disc height, the annular fibers are no longer able to provide the same degree of stability, resulting in abnormal joint motion. This excessive motion can manifest itself in abnormal muscle, ligament and tendon loading, which can ultimately be a source of back pain.
Radicular pain may result from a decrease in foraminal volume caused by decreased disc height. Specifically, as disc height decreases, the volume of the foraminal canal, through which the spinal nerve roots pass, decreases. This decrease may lead to spinal nerve impingement, with associated radiating pain and dysfunction.
Finally, adjacent segment loading increases as the disc height decreases at a given level. The discs that must bear additional loading are now susceptible to accelerated degeneration and compromise, which may eventually propagate along the destabilized spinal column.
In spite of all of these detriments that accompany decreases in disc height, where the change in disc height is gradual many of the ill effects may be “tolerable” to the spine and may allow time for the spinal system to adapt to the gradual changes. However, the sudden decrease in disc volume caused by the surgical removal of the disc or disc nucleus may heighten the local and global problems noted above. Many disc defects are treated through a surgical procedure, such as a discectomy in which the nucleus pulposus material is removed. During a total discectomy, a substantial amount (and usually all) of the volume of the nucleus pulposus is removed and immediate loss of disc height and volume can result. Even with a partial discectomy, loss of disc height can ensue. Discectomy alone is the most common spinal surgical treatment, frequently used to treat radicular pain resulting from nerve impingement by disc bulge or disc fragments contacting the spinal neural structures.
In another common spinal procedure, the discectomy may be followed by an implant procedure in which a prosthesis is introduced into the cavity left in the disc space when the nucleus material is removed. Thus far, the most prominent prosthesis is a mechanical device or a “cage” that is sized to restore the proper disc height and is configured for fixation between adjacent vertebrae. These mechanical solutions take on a variety of forms, including solid kidney-shaped implants, hollow blocks filled with bone growth material, push-in implants and threaded cylindrical cages.
In more recent years, injectable biomaterials have been more widely considered as an augment to a discectomy. As early as 1962, Alf Nachemson suggested the injection of room temperature vulcanizing silicone into a degenerated disc using an ordinary syringe. In 1974, Lemaire and others reported on the clinical experience of Schulman with an in situ polymerizable disc prosthesis. Since then, many injectable biomaterials or scaffolds have been developed as a substitute for the disc nucleus pulposus, such as hyaluronic acid, fibrin glue, alginate, elastin-like polypeptides, collagen type I gel and others. A number of patents have issued concerning various injectable biomaterials including: cross-linkable silk elastin copolymer discussed in U.S. Pat. No. 6,423,333 (Stedronsky et al.); U.S. Pat. No. 6,380,154 (Capello et al.); U.S. Pat. No. 6,355,776 (Ferrari et al.); U.S. Pat. No. 6,258,872 (Stedronsky et al.); U.S. Pat. No. 6,184,348 (Ferrari et al.); U.S. Pat. No. 6,140,072 (Ferrari et al.); U.S. Pat. No. 6,033,654 (Stedronsky et al.); U.S. Pat. No. 6,018,030 (Ferrari et al.); U.S. Pat. No. 6,015,474 (Stedronsky); U.S. Pat. No. 5,830,713 (Ferrari et al.); U.S. Pat. No. 5,817,303 (Stedronsky et al.); U.S. Pat. No. 5,808,012 (Donofrio et al.); U.S. Pat. No. 5,773,577 (Capello); U.S. Pat. No. 5,773,249 (Capello et al.); U.S. Pat. No. 5,770,697 (Ferrari et al.); U.S. Pat. No. 5,760,004 (Stedronsky); U.S. Pat. No. 5,723,588 (Donofrio); U.S. Pat. No. 5,641,648 (Ferrari); and U.S. Pat. No. 5,235,041 (Capello et al.); protein hydrogel described in U.S. Pat. No. 5,318,524 (Morse et al.); U.S. Pat. No. 5,259,971 (Morse et al.): U.S. Pat. No. 5,219,328 (Morse et al.); and U.S. Pat. No. 5,030,215; polyurethane-filled balloons discussed in 60/004,710 (Felt et al.); U.S. Pat. No. 6,306,177 (Felt et al.); U.S. Pat. No. 6,248,131 (Felt et al.) and U.S. Pat. No. 6,224,630 (Bao et al.); collagen-PEG set forth in U.S. Pat. No. 6,428,978 (Olsen et al.); U.S. Pat. No. 6,413,742 (Olsen et al.); U.S. Pat. No. 6,323,278 (Rhee et al.); U.S. Pat. No. 6,312,725 (Wallace et al.); U.S. Pat. No. 6,277,394 (Sierra); U.S. Pat. No. 6,166,130 (Rhee et al.); U.S. Pat. No. 6,165,489 (Berg et al.); U.S. Pat. No. 6,123,687 (Simonyi et al.); U.S. Pat. No. 6,111,165 (Berg); U.S. Pat. No. 6,110,484 (Sierra); U.S. Pat. No. 6,096,309 (Prior et al.); U.S. Pat. No. 6,051,648 (Rhee et al.); U.S. Pat. No. 5,997,811 (Esposito et al.); U.S. Pat. No. 5,962,648 (Berg); U.S. Pat. No. 5,936,035 (Rhee et al.); and U.S. Pat. No. 5,874,500 (Rhee et al.); chitosan in U.S. Pat. No. 6,344,488 to Chenite et al.; a variety of polymers discussed in U.S. Pat. No. 6,187,048 (Milner et al.; recombinant biomaterials in 60/038,150 (Urry); U.S. Pat. No. 6,004,782 (Daniell et al.); U.S. Pat. No. 5,064,430 (Urry); U.S. Pat. No. 4,898,962 (Urry); U.S. Pat. No. 4,870,055 (Urry); U.S. Pat. No. 4,783,523 (Urry et al.); U.S. Pat. No. 4,783,523 (Urry et al.); U.S. Pat. No. 4,589,882 (Urry); U.S. Pat. No. 4,500,700 (Urry); U.S. Pat. No. 4,474,851 (Urry); U.S. Pat. No. 4,187,852 (Urry et al.); and U.S. Pat. No. 4,132,746 (Urry et al.); and annulus repair materials described in U.S. Pat. No. 6,428,576 to Haldimann.
These references disclose biomaterials or injectable scaffolds that have one or more properties that are important to disc replacement, including strong mechanical strength, promotion of tissue formation, biodegradability, biocompatibility, sterilizability, minimal curing or setting time, optimum curing temperature, and low viscosity for easy introduction into the disc space. The scaffold must exhibit the necessary mechanical properties as well as provide physical support. It is also important that the scaffold be able to withstand the large number of loading cycles experienced by the spine. The biocompatibility of the material is of utmost importance. Neither the initial material nor any of its degradation products should elicit an unresolved immune or toxicological response, demonstrate immunogenicity, or express cytoxicity.
Generally, the above-mentioned biomaterials are injected as viscous fluids and then cured in situ. Curing methods include thermosensitive cross-linking, photopolymerization, or the addition of a solidifying or cross-linking agent. The setting time of the material is important—it should be long enough to allow for accurate placement of the biomaterial during the procedure yet should be short enough so as not to prolong the length of the surgical procedure. If the material experiences a temperature change while hardening, the increase in temperature should be small and the heat generated should not damage the surrounding tissue. The viscosity or fluidity of the material should balance the need for the substance to remain at the site of its introduction into the disc, with the ability of the surgeon to manipulate its placement, and with the need to assure complete filling of the intradiscal space or voids.
Since the intervertebral disc is an avascular structure, it relies upon the vascularized adjacent vertebral bodies to receive nutrients and expel waste. This fluid flow occurs by diffusion through the vertebral endplates. Thus, as shown in FIG. 1, a spinal disc D is disposed between adjacent vertebrae V1 and V2. The disc includes the annulus fibrosus A, which surrounds and contains the nucleus pulposus N. The portion of the adjacent vertebrae in contact with the nucleus constitutes the endplates E1 and E2.
As depicted in the figure, the bony vertebral bodies V1 and V2 are vascularized, as represented by the blood vessels B. The vertebral bodies are porous so fluid can pass to and from the vessels B. In particular, fluids traverse the semi-permeable cartilaginous endplates E1 and E2 as represented by the arrows entering and leaving the nucleus N. Fluids entering the nucleus provide nutrients to the cells of the nucleus, while fluids expelled from the disc constitute cellular metabolic waste products. The nutrients are required for cell metabolism and manufacture of extracellular matrix (e.g., collagen, proteoglycans, etc.) by the cells of the disc. This extracellular matrix provides the structure needed to resist mechanical loads and maintain normal anatomical relationships between the adjacent vertebrae. The metabolic waste products must be removed to prevent their accumulation within the disc, which build-up can lead to conditions less favorable to cell proliferation or synthesis (e.g., altered pH). Water can also diffuse through the endplates to maintain a proper intra-discal pressure, which ultimately results in an appropriate disc height.
Disc degeneration (discussed above) can result from decreases in cell nutrition and declining disc cell viability may occur through a variety of mechanisms. One common mechanism involves decreased diffusion through the adjacent vertebral endplates E1 and E2. The endplates are cartilaginous and have a thickness ranging from 0.1 mm in the region over the nucleus N to 1.6 mm at the region of the annulus fibrosus A. The endplates are also vascularized via arterioles and venous invaginations. With many types of disc degeneration, the endplates can thicken or lose vascularization, becoming increasingly impermeable and sclerotic.
As the endplates become more impermeable, diffusion through the endplates decreases. This decreased diffusion can lead to decreased transfer of nutrients to the disc cells, lower pH, reduced oxygen tension and increased cell apoptosis (programmed cell death) and necrosis. Ultimately, the altered cellular viability leads to reduced matrix synthesis by the cells of the disc. Cells under decreased nutritional influx and waste byproduct outflow are unable to synthesize the matrix needed to maintain the specialized matrix of the nucleus pulposus and inner annulus fibrosus. This specialized matrix consists of collagen and proteoglycans capable of resisting the high compressive forces exerted on the disc. The negatively charged branching structures on the large and small proteoglycans bind large amounts of water and provide for the viscoelastic properties of the healthy disc. With decreases in proteoglycan content, the intervertebral disc becomes progressively desiccated, which ultimately leads to the loss in disc height and increased instability discussed above.
Extracellular matrix forms both adjacent to the cells and distributed between the cells. The matrix distributed widely between the cells provides the overall structure needed by the nucleus pulposus to resist mechanical loading. The matrix formed adjacent to the cells (the pericellular matrix) is important in shielding the individual cells from excessive loading that could trigger gene expression changes (e.g., decreased synthesis of mRNA for matrix proteins), and could ultimately lead to cell apoptosis and necrosis. Decreased matrix synthesis in the face of poor nutrition and increased matrix breakdown by proteases, activated by the changing pH and oxygen tension, lead to progressive degeneration of the disc and increased vulnerability to repetitive trauma.
Frequently, and perhaps typically, disc degeneration and/or herniation is preceded by degeneration of the vertebral endplates. Treatment of the disc degeneration can proceed as outlined above—i.e., a discectomy followed by the introduction of some form of scaffold into the intradiscal space. In some cases, the scaffold is a solid implant or spinal fusion that does not preserve any of the mechanical properties of the disc. In many spinal fusions, the endplate is reduced to “bleeding bone” by means of a rongeur or rasp to enhance the fixation of the fusion implant to the adjacent vertebrae. In other fusion procedures, portions of the adjacent vertebrae are removed to make room for the fusion implant. In these cases, viability of the endplates is relatively unimportant.
However, where the scaffold is of the type described above that seeks to restore normal disc function (at least as much as possible), patency of the endplates is of critical concern. If the disc has sclerotic or thickened endplates, no restorative scaffold will work in its intended way because no fluid diffusion is permitted. In other words, if the foundation is deficient, the entire treatment of the disc will fall short of its goal.
Placement of cells within a matrix (or migration of cells into a matrix) is destined to fail if these cells cannot receive adequate nutrients or cannot expel metabolic products. For tissue engineering of the disc to be a viable reparative and regenerative strategy, the diseased endplate must be addressed in addition to the diseased intervertebral disc.